DESCRIPTION (Applicant's Abstract): Our primary aim of the proposed study is to document the efficacy of Behavioral Activation (BA) in the acute treatment of major depressive disorder (MDD), by comparing it to cognitive therapy (CT), Sertraline, and pill placebo (PLA). A second aim is to test the significance of the interaction between severity of MDD and response to pharmacological versus psychosocial treatments. A third aim is to determine whether or not BA and CT can prevent depressive relapse, by comparing these treatments during continuation and follow-up phases to a control group of subjects brought to remission with Sertraline and then switched to a placebo (SRD) after 16 weeks of acute treatment. A final aim is to examine the relapse prevention potential of BA and CT compared to a state-of-the-art, drug continuation regimen (SRC) for treatment responders. Our predictors are that both psychotherapies - CT and BA - as well as Sertraline will be more effective than PLA for the more severely depressed outpatients, but that the three active treatments will not be differentially effective at the end of acute treatment. At all follow-up points in time, we expect both psychotherapies - BA and CT - and SRC to be more effective at preventing relapse than SRD subjects. The implications for mental health policy are significant. Currently, pharmacotherapy constitutes the "gold standard" for maximizing the likelihood of acute treatment response. However, none of the pharmacotherapies are curative. If either BA, CT, or both prevent relapse, subjects with depression have treatment options, and medical costs may be significantly reduced. In particular, if BA, an extremely parismonious treatment, is not significantly less effective than CT after either 16 weeks of acute treatment response or at preventing relapse, we will have provided strong support that depressives can be maintained without medication at minimal costs. BA should be relatively easy to teach paraprofessional therapists, and perhaps can even be adapted to a self-administered format, because its intervention options are few, and the decision rules for implementation of particular interventions are straightforward.